期刊
GENESIS
卷 49, 期 1, 页码 24-35出版社
WILEY
DOI: 10.1002/dvg.20691
关键词
mammary gland; epithelium; Bax; apoptosis; involution; lactation
资金
- Public Health Service [CA117930]
- NATIONAL CANCER INSTITUTE [R01CA117930] Funding Source: NIH RePORTER
The mammary gland is a developmentally dynamic, hormone-responsive organ that undergoes proliferation and differentiation within the secretory epithelial compartment during pregnancy. The epithelia are maintained by pro-survival signals (e.g., Stat5, Akt1) during lactation, but undergo apoptosis during involution through inactivation of cell survival pathways and upregulation of pro-apoptotic proteins. To assess if the survival signals in the functionally differentiated mammary epithelial cells can override a pro-apoptotic signal, we generated transgenic mice that express Bax under the whey acidic protein (WAP) promoter. WAP-Bax females exhibited a lactation defect and were unable to nourish their offspring. Mammary glands demonstrated: (1) a reduction in epithelial content, (2) hallmark signs of mitochondria-mediated cell death, (3) an increase in apoptotic cells by TUNEL assay, and (4) precocious Stat3 activation. This suggests that upregulation of a single pro-apoptotic factor of the Bcl-2 family is sufficient to initiate apoptosis of functionally differentiated mammary epithelial cells in vivo. genesis 49:24-35,2011. (C) 2010 Wiley-Liss, Inc.
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